Exploiting endogenous fibrocartilage stem cells to regenerate cartilage and repair joint injury

Abstract

Tissue regeneration using stem cell-based transplantation faces many hurdles. Alternatively, therapeutically exploiting endogenous stem cells to regenerate injured or diseased tissue may circumvent these challenges. Here we show resident fibrocartilage stem cells (FCSCs) can be used to regenerate and repair cartilage. We identify FCSCs residing within the superficial zone niche in the temporomandibular joint (TMJ) condyle. A single FCSC spontaneously generates a cartilage anlage, remodels into bone and organizes a haematopoietic microenvironment. Wnt signals deplete the reservoir of FCSCs and cause cartilage degeneration. We also show that intra-articular treatment with the Wnt inhibitor sclerostin sustains the FCSC pool and regenerates cartilage in a TMJ injury model. We demonstrate the promise of exploiting resident FCSCs as a regenerative therapeutic strategy to substitute cell transplantation that could be beneficial for patients suffering from fibrocartilage injury and disease. These data prompt the examination of utilizing this strategy for other musculoskeletal tissues.

Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy

“…To determine the putative role of the vasculature in miniature pig TMJ pathology, we created a surgically induced TMJ disc perforation animal model (Figure ). We have previously published that surgically creating a perforation in the TMJ discs of rabbits leads to secondary TMJ condylar degeneration and OA . We aimed to recapitulate the TMJ disc perforation model in miniature pigs and characterize the vasculature phenotype.…”

“…TMJ osteoarthritis was surgically induced in Yucatan miniature pigs using a disc perforation model as previously described . An oblique incision was created superior to the zygomatic process.…”

Functional disorders of the temporomandibular joints: Internal derangement of the temporomandibular joint

“…This fibrocartilage tissue serves to lubricate the surfaces of motion within a TMJ during complex mechanical movements. TMJ disc and articulating surfaces may responsible for the viscoelastic compressive properties of the tissue to reduce joint friction [55–57]. However, once degenerative change starts in the TMJ, the change of ECM components and proteinases can directly or indirectly participate in the joint inflammatory processes [58,59].…”

Jaw closing movement and sex differences in temporomandibular joint energy densities

“…The molecular biological perspectives of TMJ loading should also be considered . Mechanical loads, in a dose‐dependent manner with respect to magnitude, frequency and duration, inhibit or promote molecular events responsible for cartilage health or destruction, including the synthesis of inflammatory mediators .…”

“…However, mechanical overloading can elicit oxidative stresses and inflammation leading to damage, and if the limited repair capacity of the cartilage is outstripped, then it ultimately ends in tissue failure due to mechanical fatigue. In parallel with the mechanical fatigue of the articular tissues, mechanically induced expression of inflammatory mediators disrupts localised spatial downregulation of Wnt/β‐catenin signalling which is critical for maintenance of fibrocartilage stem cells and inhibition of metalloproteinases that could otherwise challenge fibrocartilage matrix homeostasis . Why degeneration of the articular tissues occurs earlier in the TMJ compared to post‐cranial joints and why females are more afflicted than males may be due to the TMJ's unique vulnerability to combined mechanical and biological variables.…”